Assessment of ovarian follicles and serum reproductive hormones in molybdenum trioxide nanoparticles treated rats / Evaluación de folículos ováricos y hormonas reproductivas en suero de ratas tratadas con nanopartículas de trióxido de molibdeno

SUMMARY: Special features of nanoparticles have resulted in their widespread use. Small molybdenum trioxide (MoO 3) nanoparticles can translocate from the entry portals into the circulatory and lymphatic systems and ultimately to body tissues and organs depending on their composition and size. In this research, sixty Wistar rats weighting 180-250 g were divided into 6 groups (n=10) randomly: Group 1 (Control) did not receive any medicine. Group 2 (Sham) received intraperitoneal normal saline for 35 days on a daily basis. Groups 3, 4, 5 and 6 received 50, 100, 200, and 300 mg/kg MoO3, respectively, the same way in the sham group and at the same interval. At the end of the experiment, the rats were weighted again and anesthetised. Then blood samples were taken from their hearts to determine the serum levels of estrogen, progesterone, and gonadotropins. Their ovaries were removed and ovarian volume, follicular diameter, number of each follicle type, and oocyte volume were determined. Results indicated that MoO3 nanoparticles strongly reduced body and ovarian weights in the rats. Moreover, a significant decrease was observed in ovarian volume, the number of follicle types, oocyte volume and follicular diameter. The nanoparticles increased the number of atretic follicles via ovarian tissue structure. MoO3 nanoparticles decreased serum estrogen level and increased serum level of FSH that was associated with disruption in the regulation of progesterone and LH secretion. The findings showed that MoO3 nanoparticles could bear negative effects on ovarian structure and function.

RESUMEN: Las características específicas de las nanopartículas han dado lugar a su uso generalizado. Las pequeñas nanopartículas de trióxido de molibdeno (MoO3) pueden penetrar los sistemas circulatorios y linfáticos y, en última instancia, dependiendo de su composición y tamaño, también los tejidos y órganos del cuerpo. En esta investigación se dividieron 60 ratas Wistar con un peso de 180-250 g en 6 grupos (n = 10) aleatoriamente: el Grupo 1 (Control) no recibió ningún medicamento. El Grupo 2 (Sham) recibió solución salina normal intraperitoneal durante 35 días diariamente. Los grupos 3, 4, 5 y 6 recibieron 50, 100, 200 y 300 mg / kg de MoO3 respectivamente, de la misma manera en el grupo simulado, y en el mismo intervalo. Concluyendo el experimento, las ratas se pesaron nuevamente y fueron anestesiadas. Luego se tomaron muestras de sangre de los corazones para determinar los niveles séricos de estrógeno, progesterona y gonadotropinas. Se retiraron los ovarios y se determinó el volumen ovárico, el diámetro folicular, el número de cada tipo de folículo y el volumen de ovocitos. Los resultados indicaron que las nanopartículas de MoO3 redujeron significativamente los pesos corporal y ovárico en las ratas. Además, se observó una disminución importante en el volumen ovárico, el número de tipos de folículos, el volumen de ovocitos y el diámetro folicular. Las nanopartículas aumentaron el número de folículos auriculares a través de la estructura del tejido ovárico. Las nanopartículas de MoO 3 disminuyeron el nivel sérico de estrógeno y aumentaron el nivel sérico de FSH que se asoció con la interrupción en la regulación de la progesterona y la secreción de LH. Los hallazgos mostraron que las nanopartículas de MoO 3 podrían tener efectos negativos sobre la estructura y la función ovárica.

Does insulin resistance increase thyroid volume in patients with polycystic ovary syndrome?

ABSTRACT Objective To investigate the effect of gonadotropin, sex hormone levels and insulin resistance (IR) on thyroid functions and thyroid volume (TV) in polycystic ovary syndrome (PCOS). Subjects and methods 69 new diagnosed PCOS patients (age 24.82 ± 6.17) and 56 healthy control female (age 26.69 ± 5.25) were involved to the study. Fasting plasma glucose, lipid profile, insulin, thyroid stimulating hormone (TSH), free thyroxine (fT4), estradiol (E2), luteinizing hormone (LH), follicle stimulating hormone levels and urine iodine were measured in all participants. Thyroid and pelvic ultrasound were performed in all participants. Results Insulin, HOMA-IR, LH, E2 and TV were higher in PCOS group (p < 0.05). TV was significantly higher in PCOS patients with IR compared to non-IR PCOS patients (p < 0.001), while TSH, fT4, and urine iodine levels were similar between these groups (p > 0.05). There was a negative correlation between E2 and TSH (p < 0.05) and a positive correlation between TSH and TV (p < 0.05). There was a significant positive correlation between TV and LH, insulin, HOMA-IR (p < 0.05). Conclusion This study showed that TV was increased in patients with insulin resistance but differences in TSH and LH levels may affect TV changes as well.

Ovarian Leydig cell tumor in a post-menopausal patient with severe hyperandrogenism / Tumor ovariano de células de Leydig em paciente em pós-menopausa com hiperandrogenismo grave

Leydig cell tumors are rare ovarian steroid cell neoplasms. More than 75% of patients show signs of virilization due to overproduction of testosterone. We report a case of an 8-year-old woman with progressive signs of virilization, and presenting vaginal bleeding. Clinical analyses revealed high levels of serum testosterone, delta 4-androstenedione and estradiol, and also inappropriate low levels of gonadotrophins for a post-menopausal woman. Transvaginal ultrasound showed no evidence of ovarian tumor, but pelvic and abdominal computerized axial tomography imaging revealed a left ovarian solid nodule, and no evidence of alteration in the adrenal glands. Total hysterectomy and bilateral salpingoophorectomy were performed. Histopathology and immunohistochemistry confirmed the diagnosis of Leydig cell tumor. After surgery, androgen levels returned to normal, and there was regression of the signs of virilization.

Tumores ovarianos de células de Leydig são neoplasias raras de células ovarianas esteroidogênicas. Mais de 75% dos pacientes apresentam sinais de virilização devido à produção excessiva de testosterona. Relatamos aqui o caso de uma mulher de 81 anos de idade com sinais progressivos de virilização e ocorrência de sangramento vaginal. As análises clínicas mostraram altos níveis de testosterona sérica, delta 4-androstenediona e estradiol, além de níveis inadequadamente baixos de gonadotrofinas para uma mulher em pós-menopausa. O ultrassom transvaginal não apresentou evidências de tumor ovariano, mas a tomografia axial computadorizada da região pélvico-abdominal mostrou um nódulo sólido no ovário esquerdo e nenhuma evidência de alteração nas adrenais. Foi feita uma histerectomia total e salpingooforectomia bilateral. Os exames histopatológicos e a imuno-histoquímica confirmaram o diagnóstico de tumor de células de Leydig. Após a cirurgia, os níveis de androgênios voltaram ao normal, e os sinais de virilização regrediram.

Effect of ethanol extract of whole plant of Trichosanthes cucumerina var. cucumerina L. on gonadotropins, ovarian follicular kinetics and estrous cycle for screening of antifertility activity in Albino Rats / Efectos del etanol extraído de la planta completa de Trichosanthes cucumerina var. cucumerina L. sobre gonadotropinas, cinética folicular ovárica y ciclo para screening de actividad antifertilidad en Ratas Albinas

Ethanol extract of whole plant of Trichosanthes cucumerina L. var. cucumerina was evaluated for antiovulatory activity in adult rats. The ethanol extract at the doses 200 and 400mg/kg body weight (orally) affected the normal estrous cycle showing a significant increase in estrus and metestrus phases and decrease in diestras and proestrus phases. The extract also significantly reduced the number of healthy follicles (Class I-Class VI) and corpora lutea and increased the number of regressing follicles (Stage IA, Stage IB, Stage IIA, and Stage IIB). The protein and glycogen content in the ovaries were significantly reduced in treated rats. The cholesterol level was significantly increased, whereas, the enzyme activities like 3b-HSD and 17b-HSD were significantly inhibited in the ovary of treated rats. Serum FSH and LH levels were significantly reduced in the treated groups were measured by RIA. In acute toxicity test, neither mortality nor change in the behavior or any other physiological activities in mice were observed in the treated groups. In chronic toxicity studies, no mortality was recorded and there were no significant differences in the body and organ weights were observed between controls and treated rats. Hematological analysis showed no significant differences in any of the parameters examined (RBC, WBC count and Hemoglobin estimation). These observations showed the antiovulatory activity of ethanol extract of whole plant of Trichosanthes cucumerina L. var. cucumerina in female albino rats.

El extracto de etanol de toda la planta de Trichosanthes cucumerina var. cucumerina (L.) se evaluó en cuanto a su actividad antiovulatoria en ratas adultas. El extracto de etanol en dosis de 200 y 400mg/kg de peso corporal (oral) afectó el ciclo normal estral, mostrando un aumentó significativo en las fases de estro y metaestro y la disminución de las fases de diestro y proestro. El extracto también redujo significativamente el número de folículos sanos (Clase I=Clase VI) y cuerpo lúteo y aumentó el número de folículos en regresión (etapa I, etapa IB, etapa II y etapa IIB). La proteína y el contenido de glucógeno en los ovarios se redujeron significativamente en las ratas tratadas. El nivel de colesterol aumentó significativamente, mientras que, actividad de las enzimas 3b-HSD y 17b-HSD se inhibió significativamente en el ovario de ratas tratadas. FSH sérico y los niveles de LH se redujeron significativamente en los grupos tratados y medidos por RÍA. En la prueba de toxicidad aguda, no hubo mortalidad ni cambio en el comportamiento fisiológico o de cualquier otra actividad en los grupos tratados de ratas. En estudios de toxicidad crónica, no se registró mortalidad y no hubo diferencias significativas en el peso corporal o el peso de los órganos entre los controles y las ratas tratadas. Los análisis hematológicos no mostraron diferencias significativas en ninguno de los parámetros examinados (eritrocitos, recuento de glóbulos blancos y estimación de hemoglobina). Estas observaciones mostraron la actividad antiovulatoria del extracto de etanol de toda la planta de Trichosanthes cucumerina var. cucumerina en ratas albinas hembras.

Reproductive effects of human interferon-alpha-2b administration on male albino mice testes. An experimental study

Recombinant human interferon alpha [rh-IFN-alpha] is used therapeutically in malignant disorders and chronic hepatitis. The phenotypic effects of this drug at the structural levels on testicular tissue were hardly ever addressed. Hence, this work was designed in adult male albino mice to study the phenotypic effects of rh-INF-alpha-2b on testicular tissue as well as assessing its effects on serum testosterone and gonadotropins levels. This research was planned to through light on the effects of interferon-alpha-2b [IFN-alpha-2b] on the hypothalamic-pituitary-testicular [HPT] axis of the adult male albino mice. Experimental study. National Hepatology and Tropical Medicine Research Institute [NHTMRI]. The study was conducted from November [2004] to February [2005]. Thirty sexually mature male mice were divided into three groups [10 mice in each group], namely: the control, the experimental and the recovery groups. Mice in the experimental and recovery groups were administered recombinant human interferon alpha intraperitoneally at a dose of 3000 U / mouse weekly for 12 weeks in a volume of 1.0-microliter isotonic normal' saline, then animals in the recovery group were left to recover for a further period of two months. At the end of the experiment, serum concentrations of gonadotropins and testosterone were measured and then all animals were then sacrificed to study histopathologically the possible effects of interferon on the testicular tissue. rh-IFN-alpha-2b induced remarkable decline in the serum levels of both follicle stimulating hormone [FSH] and luteinizing hormone [LH] in mice of the experimental group compared to the corresponding control and mice of recovery group. At the same time, testosterone was moderately increased in the experimental group, and then returned to its normal levels within 2 months after cessation of treatment. Histopathologically, in the experimental group, there were focal thickening of the basement membrane, degenerative changes and clumping of the germinal epithelial cells in the center of seminiferous tubules, partial desquamation of the germinal epithelium from basement membrane, reduction in the germ cell height, partial arrest of maturation and increased number of Sertoli cells. Increased number of leydig's cells and hypervascularity were detected in the interstitial spaces. In the recovery group, there was lessening of the germ cell hypoplasia manifested by restoration of spermatogenic cells and accidental disruption in the basement membrane. Most of the spermatogenic and Sertoli cells restored their polarity, height and maturation. Our results suggest that rh-INF-alpha-2b temporally affects the hypothalamic-pituitary-testicular axis [HPT], both centrally and peripherally [at the testicular level], through the lessening of FSH, LH, raise of testosterone serum levels and direct phenotypic effect on the testicular tissue

[ effects of hydro alcoholic extract of dorema aucheri on blood concentration of gonadotropin and androgen hormones in adult male rats]

Dorema aucheri [Apieaceae] contains chemical compounds including flavonoids and coumarins. Flavonoids have estrogenic properties and coumarins have antiandrogenic properties. The compounds are very effective on the HPG axis. In the present study, the effect of Dorema aucheri alcoholic extract on LH, FSH, testosterone and DHT hormones on adult male rats were determined. This was an experimental study in which male adult rats were chosen and divided into 5 groups: control group which did not received any extract, sham groups which took distilled water, experimental groups, which orally took 100, 200 and 400 mg per kg of the Dorema aucheri extract for 28 consecutive days. Then the animals were weighed and the blood sample of each group was taken and used for measuring of the serum concentration of FSH, LH, DHT and testosterone. The collected data were analyzed by the SPSS software using ANOVA and t-test. The results revealed no differences in the average weight of the body and concentration of FSH hormone in the experimental group compared with the control and sham group. However significant difference was found between the concentration of LH, testosterone and dihydrotestosterone in the experimental group compared with the rest groups. Concentration of testosterone in the minimum dosage of extracts showed significant increase while significant decrease was seen in the higher dose. Significant increase was seen in the concentration of LH in all doses. DHT serum concentration in the minimum dose showed significant decrease while significant increase was seen in higher dosage. It seems that the flavonoids compound of Dorema aucheri extract caused the LH hormone to increase prolactin. Using the extract increases the LH hormone and inhibition of aromatase and 5 alfa reductase enzymes cause the testosterone and DHT hormone to increase in higher dosage

Serum sex steroids, gonadotrophins and sex hormone-binding globulin in prostatic hyperplasia

Benign prostatic hyperplasia [BPH] develops in elderly males when serum androgens are relatively lower than in healthy younger males, but it is not well understood whether and how sex steroids are altered in prostatic hyperplasia. It is also uncertain whether there is any change in sex steroid levels in males older than 40 years of age. The use of androgens in elderly males is often discouraged because of the probable worsening effect of androgens on prostatism. This study aimed to determine the relationship between prostatic hyperplasia and sex steroid levels and whether there is any significant change in these hormones after the age of 40 years. We studied healthy males of age 240 years with [n=92] or without [n=93] clinical prostatic hyperplasia. Serum testosterone, estradiol, gonadotrophins and sex hormone-binding globulin [SHBG] were compared. The hormones and SHBG were also correlated with age. No significant difference was found in any hormone in cases with prostatic hyperplasia as compared with the controls. There was no significant age-related change in any hormone except estradiol where as a negative correlation [P<.003] with age was found. Serum sex steroids and SHBG remained unchanged in symptomatic prostatic hyperplasia and except for estradiol there was no significant age-related change in serum testosterone, gonadotrophins and SHBG in healthy males after the fourth decade. More studies are needed to confirm the age-related decline of estrogens in males

Correlation between seminal fluid analysis and levels of gonadotropins in serum and seminal plasma of normozoospermic men and infertile patients

Levels of serum gonadotropins have direct effects on testicular functions and spermatogenesis. Assessment of levels of serum gonadotropins from fathered subjects and infertile patients indicates wide range diversity. In this study, we tried to find out whether the levels of seminal FSH and LH affect the parameters of seminal fluid analysis [SFA] and if there is any correlation between levels of serum FSH and LH in healthy men and infertile patients. Levels of FSH and LH in serum and seminal plasma were assessed randomly, in addition to examination of seminal fluid analysis from 12 normozoospermic subjects [age range: 33-56 years] and 66 infertile patients [age range: 20-62 years] with duration of infertility [15-201 months]. Macroscopic and microscopic parameters of semen specimens were determined. Data were statistically analyzed using multiple correlation and regression, and MANOVA tests. Result of the present study observed significant positive correlation between FSH levels in serum and seminal plasma [r=0.984; p<0.001] of normozoospermic subjects as compared to other groups of infertile patients. No correlations were noticed between LH levels in serum and seminal plasma of normozoospermic subjects and groups of infertile patients. Significant and positive correlation was assessed between sperm concentration and levels of seminal FSH [r=0.822; p<0.05 and r=0.940; p<0.01] and seminal LH [r=0.989; p<0.001 and r=0.999; p<0.001] of asthenozoospermic and OAT patients respectively. In asthenozoospermic patients, significant and positive correlations were observed between seminal FSH and percentages of sperm motility, progressive motility, sperm normal morphology and total progressive motile sperm/ejaculate. This study shows a strong association and effect between seminal FSH and serum FSH and parameters of SFA for normozoospermic men and different groups of infertile patients. These finding may call for large cohorts being executed with larger population of patients that is required for this analysis to be more accurate

Activity of follicular fluid phosphatases and their correlation with levels of serum esteroidal hormones and gonadotropins

The aim of this study was to evaluate the correlation between serum levels of ovarian and gonadotropin hormones, age and number of follicles with follicular alkaline and acid phosphatase activity in infertile women under controlled ovarian hyperstimulation. After collection of follicular fluid and calculation of the number of follicles, the specific activity of alkaline [ALP] and acid phosphatase [ACP] was determined according to the total protein in 19 women at the time of puncture. Also at that time, the levels of progesterone, estradiol, and follicle stimulating hormone [FSH] and leuteinizing hormone [LH] of their sera were measured. The correlation of follicular ALP and ACP with each serum hormone levels, women age and number of follicles was calculated using non-parametric analysis. The ALP has a correlation with progesterone [P=0.01] levels but doesn't have any correlation with the other factors. However, the ACP activity has a correlation not only with follicular number but also with estradiol and progesterone levels [P=0.05]. Thus ACP activity is more affected by ovarian hormone than ALP and it can affect the ovarian microenvironment and oocyte development

Seasonal effects of melatonin on ovary and plasma gonadotropin and vitellogenin levels in intact and pinealectomized catfish, Clarias batrachus (Linn).

Effects of daily administration of melatonin for 15 days were evaluated with respect to ovarian activities and plasma gonadotropin (GtH II) and vitellogenin (Vg) levels in intact (INT) and pinealectomized (Px) female catfish, C. batrachus, during preparatory (April), prespawning (May and June), spawning (July) and post-spawning (September) periods. Px (saline control groups) caused a stimulatory effect during preparatory (with respect to Vg synthesis and incorporation) and prespawning (with respect to Vg synthesis) periods whereas no effect was observed during spawning and post-spawning periods with respect to the reproductive parameters studied. During April, melatonin-treatment significantly decreased plasma GtH II levels and percentage of vitellogenic oocytes without any significant changes in plasma Vg levels and gonadosomatic index (GSI). During early prespawning period, in May, 50microg melatonin brought about a significant reduction in plasma GtH II levels in INT group, whereas 100microg caused a decrease in all parameters; on the other hand, in Px groups both dose levels proved to be inhibitory. In June (late prespawning period) melatonin-treatment could not bring about any change in GSI and plasma Vg levels compared to the control groups regardless of Px but plasma GtH II and mean number of yolky oocytes were significantly reduced in melatonin-treated INT group. During spawning period (July) melatonin inhibited the GSI, mean number of yolky oocytes and plasma GtH II levels without affecting plasma Vg levels. In September (post-spawning period), melatonin did inhibit both GSI and plasma GtH II levels. The results, thus, indicate that melatonin showed variable effects (inhibitory and/or no effect) to GSI, mean number of yolky oocytes and plasma Vg levels but a consistent inhibiton of plasma GtH II levels indicating that melatonin may control the reproduction by blocking the GtH II release from the pituitary via affecting the hypothalamo-hypophysial axis.

Evaluation of the gonadotropic ratios among men with varying sperm quality

This study was designed to determine the levels of serum LH and FSH, along with their ratios, among men with varying sperm quality. One hundred fifty married men, presenting with a complaint of infertility, which had been evaluated for their seminal profile, and had been classified as azoospermic [50], oligozoospermic [50], asthenozoospermic [20] and normozoospermic [30] were studied for the analysis of serum LH, FSH, levels using Enzyme Immuno Assay [EIA]. Data were compared using student "t-test. The FSH and LH level indicated inverse/negative correlation to sperm concentration. The mean FSH and LH levels for the groups were 22.92 +/- 4.15 and 13.85 +/- 2.33 [Azoospermia], 16.82 +/- 3.79 and 10.92 +/- 3.79 [Oligozoospermia], 3.22 +/- 0.61 and 3.92 +/- 1.17 [Asthenozoospermia] while the levels in normozoospermic men were 5.53 +/- 0.52 and 7.40 +/- 0.60. Similarly, the LH/FSH and FSH/LH ratios in the four groups were 0.77 +/- 0.08 and 1.84 +/- 0.22 [Azoospermia], 1.78 +/- 0.41 and 1.47 +/- 0.18 [Oligozoospermia], 1.51 +/- 0.46 and 1.28 +/- 0.28 [Asthenozoospermia] and the respective ratios in normozoospermic men were 1.55 +/- 0.16 and 0.85 +/- 0.10. The present data indicate that disturbance in gonadotropin ratios also causes infertility, since these hormones act synergistically.

McCune Albright Syndrome (MCAS): a case series.

McCune Albright Syndrome (MCAS) is an association of, Café-au-lait macules, polyostotic fibrous dysplasia and autonomous hyperfunctioning endocrinopathy. This is a rare disorder seen more commonly in females. We evaluated 7 (6F & 1M) cases under six years of age (4 months to 5.5 yrs) presenting with Café-au-lait spots, polyostotic fibrous dysplasia and/or sexual precocity. All the 7 cases had large Café-au-lait spots, radiologic features of polyostotic fibrous dysplasia were seen in 5 cases. Six girls had precocious puberty with large ovarian follicles and elevated S. Estradiol levels (14-65 pg/dl) with prepubertal gonadotropin levels in 5 of them. Medroxy-progrestrone acetate was used to treat the sexual precocity. Five girls on follow up for 6 months (6mo-16mo) showed cessation of menstrual episodes and regression of ovarian follicles in three, regression in breast size in one, and three girls continued to grow at a height velocity >95th centile for age. Skeletal lesions and skin features did not show any change. No other endocrinopathy was noted. Gonadotropin independent precocious puberty was the only endocrine affection seen in this series.

Polycystic ovary syndrome [PCOS] - the highly significant associated hormonal and biochemical parameters in normal and polycystic-appearing ovary groups

To evaluate what hormonal and/or biochemical parameters are highly associated with polycystic ovary syndrome [PCOS] in ultrasonically normal and polysticappearing ovary groups. A prospective randomized comparative study El Galaa Maternity Teaching Hospital Patients[s]: Thirty two women fulfilling the entry diagnostic criteria for PCOS were randomly subdivided into two groups-group I [n=16] with ultrasonically normal-appearing ovaries and group II [n=16] with characteristic polycystic ovarian morphology. The two groups were matched for age and body mass index [BMI]. All patients had elevated serum testosterone [T] level between 80 and 150 ng/dL i.e. androgen excess. Insulin infusion for the purpose of performing insulin tolerance testing to evaluate insulin resistance or sensitivity. We measured serum androgens [T, DHEAS and androstenedione], gonadotorophins [FSH and LH], binding proteins [sex hormone-bending globulin SHBG and insulin-like growth factor binding protein-1, IGFBP-1], insulin-like growth factor-1 [IGF-1] and insulin resistance by insulin tolerance testing [ITT]. Serum androgens and binding proteins were not significant different in both groups. Insulin tolerance testing demonstreated a slower glucose disappearance in the polycystic-appearing ovary group. K-itt] glucose was 4.58% +/- 1.4% / min and 2.07% +/- 1.07% min in the normal and polucystic-appearing ovaries group respectively. Women with PCOS and polcystic ovarian morphology do not demonstrate any definitive serum hormonal differences compared with women with PCOS and normal-appearing ovaries. The presence of polycystic-appearing ovaries correlates significantly with the presence of insulin resistance, a findings that highlights the long-term health consequences of the syndrome

Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10), hypothyroid (N = 10), treated with 0.05 percent 6-propyl-2-thiouracil (PTU) in drinking water for 60 days, and T4-treated group (N = 10), receiving daily sc injections of L-thyroxine (0.8 æg/100 g body weight) during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71 percent of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72 percent of controls and only in 34 percent of hypothyroid and 43 percent of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed

A study of insulin resistance in subjects with acanthosis nigricans.

AIM: To study the prevalence of insulin resistance (IR) and its sequelae in patients with acanthosis. METHODOLOGY: Thirty six patients (28 females; eight males) with biopsy proven acanthosis nigricans and eight controls were evaluated for insulin sensitivity (IS) by estimating (a) the glucose and insulin responses to a 75 gm glucose load (Oral glucose tolerance test-OGTT), (b) the glucose disposal rate (GDR) during an intravenous insulin tolerance test (ITT). Serum androgen levels (testosterone--Te, androstenedione--ASD, Dehydro-epiandrosterone sulphate--DHEAS) were estimated in the basal state and 60 min after a bolus of insulin. Thyroid function tests (tri-iodo-thyronine--T3, thyroxine--T4, thyroid stimulating hormone--TSH) were performed in all subjects. RESULTS: The acanthotic population, overall had insignificant hyperglycemia (Area under curve of glucose--AUC-G : 17,745.5 +/- 847.5 v/s 11,051.3 +/- 274.5 mg/dl/min) and hyperinsulinemia (Area under curve of insulin -AUC-I: 20,825.2 +/- 1,287.7 v/s 6,340.1 +/- 984.2 microlU/ml/min) compared to controls during OGTT. Eight patients with acanthosis nigricans had impaired glucose tolerance and eight had overt diabetes using WHO criteria. 69.4% of the acanthotic subjects were obese and 13.9% (5/36) were hypertensive. Thyroid dysfunction was present in three (one had hypothyroidism and two had thyrotoxicosis). Reproductive disorders--menstrual irregularity (46.5%), amenorrhea (21.4%), hirsuitism (21.4%) and infertility (3.6%) was encountered in a significant number of acanthotics. Acanthotics overall had statistically higher levels of androgens; Te (females)--0.74 +/- 0.09 v/s 0.27 +/- 0.09 ng/ml (p < 0.005), ASD--1.8 +/- 0.21 v/s 0.94 +/- 0.2 ng/ml (p < 0.005) and DHEAS--1,880.8 +/- 216.3 v/s 772.8 +/- 210.4 ng/ml (p < 0.005). An elevated DHEAS correlated positively to body mass index (BMI) and android obesity. Serum Te levels correlated positively with GDR. Serum insulin levels increased progressively with obesity and acanthosis. Serum insulin was associated with progressive worsening of hyperandrogenism (as seen in non-obese controls, non-obese and obese acanthotics). CONCLUSIONS: Subjects with acanthosis nigricans should be screened for insulin resistance and its clinical and metabolic sequelae. Thyroid dysfunction should be sought in these subjects as it can be easily treated.

Esteróides sexuais e gonadotrofinas em mulheres com e sem carcinoma de endométrio: um estudo clínico comparativo / Endogenous sexual steroids and gonadotrophins in women with or without endometrial carcinoma: a comparative clinical study

Objetivo: analisar os níveis dos esteróides sexuais endógenos e gonadotrofinas em mulheres com e sem câncer de endométrio. Métodos: foi realizado estudo clínico-comparativo com 20 mulheres na pós-menopausa com câncer de endométrio e 20 mulheres na pós-menopausa, sem câncer de endométrio. A idade, o tempo de menopausa e o índice de massa corpórea foram utilizados como variáveis de emparelhamento. Os níveis plasmáticos dos esteróides sexuais endógenos froam medidos por métodos de radioimunoensaio e imunoenzimático. Para análise estatística utilizamos o teste "t" de Student. Resultados: os níveis de androstenediona (A), testosterona total (t) e testosterona livre (TL) foram mais elevados nas mulheres com câncer de endométrio e os níveis de hormônio luteinizante (LH) foram significativamente menores nessas mulheres. Também observados que a razão (E1/A) mostrou valores significativamente menores no grupo de mulheres com câncer, ao passo que a razão E2/E1) não apresentou diferenças nos dois grupos. Conclusões: destacamos a potencialidade dos esteróides sexuais e gonadotrofinas na gênese do adenocarcinoma de endométrio em mulheres na pós-menopausa.

¿Modulan los andrógenos la secreción de hormona luteinizante en mujeres? / Do androgens modulate luteinizing hormone secretion in women?

In hiperandrogenic states an abnormal pattern of LH secretion in women is observed, which is presumed to result from a direct action of androgen or its conversion to estrogen. Two strategies are available to study the effect of testosterona on LH secretion.One involves the use of non-steroidal compounds that block the negative feedback actions of endogenous androgens by binding to androgen receptors; the other consists only in the administration of androgens. Following these two strategies, we first studies the pulsatile gonadotrophin secretion in hyperandrogenic women, following flutamide administration, a specific androgen receptor blocker. Flutamide treatment was followed by a decrease in LH pulse amplitude and mean LH concentrations, demonstrating that androgen receptor blockade reduces LH secretion in hyperandrogenic women. To establish the level at which the androgen effect is exerted, we further studied the acute effect of testosterone (hyperandrogenic levels) and the blockade of its receptor on LH secretion in patients with severe hypothalamic deficiency treated with pulsatile GnRH (GnRHp). LH pulse profiles were assessed under GnRHp treatment alone, during testosterone and during testosterone and flutamide administration. Testosterone increased LH secretion and LH pulse amplitud. Flutamide significantly reverted the LH increase induced by testosterone.These results strongly suggest that testosterone in the hyperandrogenic female range, may facilitate LH secretion by the pituitary, effect that is reserved by the blockade of the androgen receptor

Hiperandrogenismo en la Mujer y su Relacion con los Androgenos y las Hormonas del Eje Gonadal / Hyperandrogenism in women and its relationship with androgens and hormones of the gonadal axis

Se estudiaron 42 pacientes con un indice de hirsutismo >= 15 (metodo de Ferriman-Gallwey) para conocer con que frecuencia se elevan en ellas los androgenos, precisar su volumen ovarico, la presencia de microquistes y los niveles de gonadotropinas y estradiol. Se dividieron las pacientes en 3 grupos: a) Hiperandrogenismo clinico, aquellas con todos los androgenos normales; b) Hiperandrogenismo clinico-quimico, aquellas con 1 o mas androgenos elevados y c) Total de pacientes. Se tomo muestra de sangre para determinar androgenos, FSH, LH, estradiol y prolactina. Se realizo un ultrasonido abdominal para medir ambos ovarios. Se correlacionaron los androgenos con las hormonas que miden funcionalidad del eje gonadal y se compararon los resultados entre los grupos. Se utilizo la prueba de U de Mann-Whitney y la de chi-cuadrado para analisis estadistico mediante el paquete SPSSPC. Se encontro el 64,2 por ciento de HACQ entre las pacientes con alta frecuencia de alteracion de mas de 1 androgeno (44,4 por ciento); la A'diona y la T fueron las mas comunmente elevadas. La media del indice de masa corporal fue similar en los distintos grupos. Todos los pacientes en las que el ultrasonido resulto normal tenian un indice LH/FSH anormal. Existe alta frecuencia de alteracion de 1 o mas androgenos en las pacientes que se consultan por hirsutismo moderado o severo; el aumento de tamano de los ovarios es indicador para el diagnostico de alteraciones en la secrecion de gonadotropinas; la obesidad no es un hallazgo frecuente y, en ocasiones, los estados de hiperandrogenismo se asocian con hiperprolactinemia